The native or normal prion protein, designated PrP or PrPc, for the cellular prion protein is a glycoprotein broadly expressed in the lymphoid and neuronal cells of mammals.
Conformational changes of PrPc result in the appearance and the propagation of the protein pathogen PrPc, that is resistant to the proteinase K. This protein pathogen can be indifferently called PrPsc or PrPres. Accumulation of PrPsc in the organs of animals is at the origin of numerous diseases and especially trembling in small ruminants, of chronic cachetic disease (or chronic wasting disease “CWD”) of the elk and antelope, bovine spongiform encephalopathy (ESB) and Creutzfeld-Jakob disease (MCJ) in humans.
The delayed appearance after an incubation period of 2 to 6 years and the slow development of symptoms in cattle infected with ESB has considerably slowed the development of epidemiological models. ESB is transmissible by ingestion to humans and has resulted in the appearance of a new form of Creutzfeld-Jakob disease (vMJC).
Detecting the protein pathogen PrPsc is difficult in infected animals that are otherwise healthy before the development of the disease and especially in the blood and urine of diseased animals. It has been established that PrPsc present in animals intended for human consumption is transmitted to humans during the ingestion of infected tissues. Thus, a major objective of public health is to avoid this transmission by detecting the presence of PrPsc:
In animals intended for human consumption to remove them from the food chain;
In blood donations and blood derivatives intended for transfusion to humans. In fact, as the presence of the protein pathogen PrPsc in the blood and the lymphoid liquids shows well before the cerebral disturbance, and thus well before the possibility of detecting the neurological signs suggestive of a clinically declared prion disease, the physiopathology in humans is poorly recognized and, not being able to carry out experimental infections as in sheep, the absence of a detection test in the blood or another biological fluids does not allow it to be studied and to thus prevent human to human transmission by blood donation or to treat infected persons before the cerebral lesions have begun; and
In animal herds before the neurological stage, thus permitting the elimination of animals infected early before their arrival in the slaughterhouse.
Detecting the presence of PrPsc in biological samples or animals has thus become extremely important and several research teams are developing methods of immunological detections (WO 02/086551). Moreover, methods of complexing peptides, small molecules or inhibittors to PrPsc to treat vMJC constitute the subject of active research. However, those methods constantly come up against the difficulty of identifying PrPsc in a reliable manner when it is in a low quantity in a biological sample and especially in biological fluids.